Circumcision is associated with significant reductions in HIV, HSV-2 and HPV infections among men and significant reductions in bacterial vaginosis among their female partners.
We assessed the penile ...(coronal sulci) microbiota in 12 HIV-negative Ugandan men before and after circumcision. Microbiota were characterized using sequence-tagged 16S rRNA gene pyrosequencing targeting the V3-V4 hypervariable regions. Taxonomic classification was performed using the RDP Naïve Bayesian Classifier. Among the 42 unique bacterial families identified, Pseudomonadaceae and Oxalobactericeae were the most abundant irrespective of circumcision status. Circumcision was associated with a significant change in the overall microbiota (PerMANOVA p = 0.007) and with a significant decrease in putative anaerobic bacterial families (Wilcoxon Signed-Rank test p = 0.014). Specifically, two families-Clostridiales Family XI (p = 0.006) and Prevotellaceae (p = 0.006)-were uniquely abundant before circumcision. Within these families we identified a number of anaerobic genera previously associated with bacterial vaginosis including: Anaerococcus spp., Finegoldia spp., Peptoniphilus spp., and Prevotella spp.
The anoxic microenvironment of the subpreputial space may support pro-inflammatory anaerobes that can activate Langerhans cells to present HIV to CD4 cells in draining lymph nodes. Thus, the reduction in putative anaerobic bacteria after circumcision may play a role in protection from HIV and other sexually transmitted diseases.
BackgroundWe estimated rates of human immunodeficiency virus (HIV)–1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner MethodsWe retrospectively ...identified 235 monogamous, HIV-discordant couples in a Ugandan population-based cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner’s stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression ResultsThe average rate of HIV transmission was 0.0082/coital act (95% confidence interval CI, 0.0039–0.0150) within ∼2.5 months after seroconversion of the index partner; 0.0015/coital act within 6–15 months after seroconversion of the index partner (95% CI, 0.0002–0.0055); 0.0007/coital act (95% CI, 0.0005–0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015–0.0041) 6–25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission ConclusionsThe rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission
HIV self-testing may encourage greater uptake of testing, particularly among key populations and other high-risk groups, but local community perceptions will influence test uptake and use. We ...conducted 33 in-depth interviews and 6 focus group discussions with healthcare providers and community members in high-risk fishing communities (including sex workers and fishermen) and lower-risk mainland communities in rural Uganda to evaluate values and preferences around HIV self-testing. While most participants were unfamiliar with HIV self-testing, they cited a range of potential benefits, including privacy, convenience, and ability to test before sex. Concerns focused on the absence of a health professional, risks of careless kit disposal and limited linkage to care. Participants also discussed issues of kit distribution strategies and cost, among others. Ultimately, most participants concluded that benefits outweighed risks. Our findings suggest a potential role for HIV self-testing across populations in these settings, particularly among these key populations. Program implementers will need to consider how to balance HIV self-testing accessibility with necessary professional support.
Uganda has one of the highest rates of alcohol use in sub-Saharan Africa but prevalence and correlates of drinking are undocumented in the Rakai region, one of the earliest epicenters of the HIV/AIDS ...epidemic in East Africa.
We analyzed cross-sectional data from 18,700 persons (8,690 men, 10,010 women) aged 15-49 years, living in agrarian, trading and fishing communities and participating in the Rakai Community Cohort Study (RCCS) between March 2015 and September 2016. Logistic regression models assessed associations between past year alcohol use and sociodemographic characteristics, other drug use and HIV status, controlling for age, religion, education, occupation, marital status, and household socioeconomic status.
Past year alcohol prevalence was 45%. Odds of drinking were significantly higher in men (versus women) and fishing communities (versus agrarian areas). Odds of drinking increased with age, previous (versus current) marriage and past year drug use. By occupation, highest odds of drinking were among fishermen and (in women) bar/restaurant workers. Alcohol-related consequences were more commonly reported by male (vs. females) drinkers, among whom up to 35% reported alcohol dependence symptoms (e.g., unsteady gait). HIV status was strongly associated with alcohol use in unadjusted but not adjusted models.
Alcohol use differed by gender, community type and occupation. Being male, living in a fishing community and working as a fisherman or restaurant/bar worker (among women) were associated with higher odds of drinking. Alcohol reduction programs should be implemented in Uganda's fishing communities and among people working in high risk occupations (e.g., fishermen and restaurant/bar workers).
Summary Background Ecological and observational studies suggest that male circumcision reduces the risk of HIV acquisition in men. Our aim was to investigate the effect of male circumcision on HIV ...incidence in men. Methods 4996 uncircumcised, HIV-negative men aged 15–49 years who agreed to HIV testing and counselling were enrolled in this randomised trial in rural Rakai district, Uganda. Men were randomly assigned to receive immediate circumcision (n=2474) or circumcision delayed for 24 months (2522). HIV testing, physical examination, and interviews were repeated at 6, 12, and 24 month follow-up visits. The primary outcome was HIV incidence. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov , with the number NCT00425984. Findings Baseline characteristics of the men in the intervention and control groups were much the same at enrolment. Retention rates were much the same in the two groups, with 90–92% of participants retained at all time points. In the modified intention-to-treat analysis, HIV incidence over 24 months was 0·66 cases per 100 person-years in the intervention group and 1·33 cases per 100 person-years in the control group (estimated efficacy of intervention 51%, 95% CI 16–72; p=0·006). The as-treated efficacy was 55% (95% CI 22–75; p=0·002); efficacy from the Kaplan-Meier time-to-HIV-detection as-treated analysis was 60% (30–77; p=0·003). HIV incidence was lower in the intervention group than it was in the control group in all sociodemographic, behavioural, and sexually transmitted disease symptom subgroups. Moderate or severe adverse events occurred in 84 (3·6%) circumcisions; all resolved with treatment. Behaviours were much the same in both groups during follow-up. Interpretation Male circumcision reduced HIV incidence in men without behavioural disinhibition. Circumcision can be recommended for HIV prevention in men.
HIV prevalence varies markedly throughout Africa, and it is often presumed areas of higher HIV prevalence (i.e., hotspots) serve as sources of infection to neighboring areas of lower prevalence. ...However, the small-scale geography of migration networks and movement of HIV-positive individuals between communities is poorly understood. Here, we use population-based data from ~22,000 persons of known HIV status to characterize migratory patterns and their relationship to HIV among 38 communities in Rakai, Uganda with HIV prevalence ranging from 9 to 43%. We find that migrants moving into hotspots had significantly higher HIV prevalence than migrants moving elsewhere, but out-migration from hotspots was geographically dispersed, contributing minimally to HIV burden in destination locations. Our results challenge the assumption that high prevalence hotspots are drivers of transmission in regional epidemics, instead suggesting that migrants with high HIV prevalence, particularly women, selectively migrate to these areas.
Summary The promise of combination HIV prevention—the application of multiple HIV prevention interventions to maximise population-level effects—has never been greater. However, to succeed in ...achieving significant reductions in HIV incidence, an additional concept needs to be considered: combination implementation. Combination implementation for HIV prevention is the pragmatic, localised application of evidence-based strategies to enable high sustained uptake and quality of interventions for prevention of HIV. In this Review, we explore diverse implementation strategies including HIV testing and counselling models, task shifting, linkage to and retention in care, antiretroviral therapy support, behaviour change, demand creation, and structural interventions, and discusses how they could be used to complement HIV prevention efforts such as medical male circumcision and treatment as prevention. HIV prevention and treatment have arrived at a pivotal moment when combination efforts might result in substantial enough population-level effects to reverse the epidemic and drive towards elimination of HIV. Only through careful consideration of how to implement and operationalise HIV prevention interventions will the HIV community be able to move from clinical trial evidence to population-level effects.
Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the ...prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men.
We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2-seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months.
At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval CI, 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44).
In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure. (ClinicalTrials.gov numbers, NCT00425984 and NCT00124878.)
The efficacy of male circumcision for HIV prevention over 2 years has been demonstrated in three randomized trials, but the longer-term effectiveness of male circumcision is unknown.
We conducted a ...randomized trial of male circumcision in 4996 HIV-negative men aged 15-49 in Rakai, Uganda. Following trial closure, we offered male circumcision to control participants and have maintained surveillance for up to 4.79 years. HIV incidence per 100 person-years was assessed in an as-treated analysis, and the effectiveness of male circumcision was estimated using Cox regression models, adjusted for sociodemographic and time-dependent sexual behaviors. For men uncircumcised at trial closure, sexual risk behaviors at the last trial and first posttrial visits were assessed by subsequent circumcision acceptance to detect behavioral risk compensation.
By 15 December 2010, 78.4% of uncircumcised trial participants accepted male circumcision following trial closure. During posttrial surveillance, overall HIV incidence was 0.50/100 person-years in circumcised men and 1.93/100 person-years in uncircumcised men {adjusted effectiveness 73% 95% confidence interval (CI) 55-84%}. In control arm participants, posttrial HIV incidence was 0.54/100 person-years in circumcised and 1.71/100 person-years in uncircumcised men adjusted effectiveness 67% (95% CI 38-83%). There were no significant differences in sociodemographic characteristics and sexual behaviors between controls accepting male circumcision and those remaining uncircumcised.
High effectiveness of male circumcision for HIV prevention was maintained for almost 5 years following trial closure. There was no self-selection or evidence of behavioral risk compensation associated with posttrial male circumcision acceptance.
Individual susceptibility to HIV is heterogeneous, but the biological mechanisms explaining differences are incompletely understood. We hypothesized that penile inflammation may increase HIV ...susceptibility in men by recruiting permissive CD4 T cells, and that male circumcision may decrease HIV susceptibility in part by reducing genital inflammation. We used multi-array technology to measure levels of seven cytokines in coronal sulcus (penile) swabs collected longitudinally from initially uncircumcised men enrolled in a randomized trial of circumcision in Rakai, Uganda. Coronal sulcus cytokine levels were compared between men who acquired HIV and controls who remained seronegative. Cytokines were also compared within men before and after circumcision, and correlated with CD4 T cells subsets in foreskin tissue. HIV acquisition was associated with detectable coronal sulcus Interleukin-8 (IL-8 aOR 2.26, 95%CI 1.04-6.40) and Monokine Induced by γ-interferon (MIG aOR 2.72, 95%CI 1.15-8.06) at the visit prior to seroconversion, and the odds of seroconversion increased with detection of multiple cytokines. Coronal sulcus chemokine levels were not correlated with those in the vagina of a man's female sex partner. The detection of IL-8 in swabs was significantly reduced 6 months after circumcision (PRR 0.59, 95%CI 0.44-0.87), and continued to decline for at least two years (PRR 0.29, 95%CI 0.16-0.54). Finally, prepuce IL-8 correlated with increased HIV target cell density in foreskin tissues, including highly susceptible CD4 T cells subsets, as well as with tissue neutrophil density. Together, these data suggest that penile inflammation increases HIV susceptibility and is reduced by circumcision.
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